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A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats

Developing a new drug delivery system is one of the useful approaches to overcome the limited use of berberine (BBR) to enhance its absorption and bioavailability. We prepared a novel berberine–glycyrrhizic acid (BBR–GL) complex formulation to increase the plasma concentration and bioavailability of...

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Autores principales: Zhang, Shichang, Zhao, Yiwei, Tan, Liangjun, Wu, Sheng, Zhang, Qing, Zhao, Boxin, Li, Guofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353711/
https://www.ncbi.nlm.nih.gov/pubmed/35935857
http://dx.doi.org/10.3389/fphar.2022.891829
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author Zhang, Shichang
Zhao, Yiwei
Tan, Liangjun
Wu, Sheng
Zhang, Qing
Zhao, Boxin
Li, Guofeng
author_facet Zhang, Shichang
Zhao, Yiwei
Tan, Liangjun
Wu, Sheng
Zhang, Qing
Zhao, Boxin
Li, Guofeng
author_sort Zhang, Shichang
collection PubMed
description Developing a new drug delivery system is one of the useful approaches to overcome the limited use of berberine (BBR) to enhance its absorption and bioavailability. We prepared a novel berberine–glycyrrhizic acid (BBR–GL) complex formulation to increase the plasma concentration and bioavailability of BBR by improving BBR solubility and lowering the absorption barrier. The complex formulation with BBR and GL in the ratio 1:1 was developed through the self-assembly process and evaluated in vitro. Compared with BBR and BBR/GL physical mixture, the BBR–GL complex showed different characteristics by SEM, DSC, FT-IR, and PXRD measurement. In pharmacokinetic evaluation, the BBR–GL complex significantly increased the plasma concentration of BBR and the major metabolite berberrubine (BBB), with the AUC of BBR elevated to 4.43-folds, while the complex was safe as BBR. Furthermore, doxorubicin (DOX) was used to induce cardiotoxicity. Hematological study, histopathological examinations, electrocardiography (ECG), cardiac secretion measurement, and biochemical index analysis proved that the model of doxorubicin-induced cardiotoxicity (DIC) was conducted successfully. With the AUC of BBR increasing in the BBR–GL complex and the absorbed complex itself, the BBR–GL complex enhanced prevention effect to DIC and exhibited a significant prevention effect to attenuate heart damage. Our findings demonstrated that a novel BBR-loaded BBR–GL complex formulation could increase BBR plasma concentration. Improvement of BBR bioavailability by the BBR–GL complex could coordinate with GL to attenuate DIC. Concerning the safety of the drug delivery system at present, the BBR–GL complex could be a potential therapeutic formulation for the prevention of cardiac damage in the clinical application of doxorubicin.
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spelling pubmed-93537112022-08-06 A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats Zhang, Shichang Zhao, Yiwei Tan, Liangjun Wu, Sheng Zhang, Qing Zhao, Boxin Li, Guofeng Front Pharmacol Pharmacology Developing a new drug delivery system is one of the useful approaches to overcome the limited use of berberine (BBR) to enhance its absorption and bioavailability. We prepared a novel berberine–glycyrrhizic acid (BBR–GL) complex formulation to increase the plasma concentration and bioavailability of BBR by improving BBR solubility and lowering the absorption barrier. The complex formulation with BBR and GL in the ratio 1:1 was developed through the self-assembly process and evaluated in vitro. Compared with BBR and BBR/GL physical mixture, the BBR–GL complex showed different characteristics by SEM, DSC, FT-IR, and PXRD measurement. In pharmacokinetic evaluation, the BBR–GL complex significantly increased the plasma concentration of BBR and the major metabolite berberrubine (BBB), with the AUC of BBR elevated to 4.43-folds, while the complex was safe as BBR. Furthermore, doxorubicin (DOX) was used to induce cardiotoxicity. Hematological study, histopathological examinations, electrocardiography (ECG), cardiac secretion measurement, and biochemical index analysis proved that the model of doxorubicin-induced cardiotoxicity (DIC) was conducted successfully. With the AUC of BBR increasing in the BBR–GL complex and the absorbed complex itself, the BBR–GL complex enhanced prevention effect to DIC and exhibited a significant prevention effect to attenuate heart damage. Our findings demonstrated that a novel BBR-loaded BBR–GL complex formulation could increase BBR plasma concentration. Improvement of BBR bioavailability by the BBR–GL complex could coordinate with GL to attenuate DIC. Concerning the safety of the drug delivery system at present, the BBR–GL complex could be a potential therapeutic formulation for the prevention of cardiac damage in the clinical application of doxorubicin. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9353711/ /pubmed/35935857 http://dx.doi.org/10.3389/fphar.2022.891829 Text en Copyright © 2022 Zhang, Zhao, Tan, Wu, Zhang, Zhao and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Shichang
Zhao, Yiwei
Tan, Liangjun
Wu, Sheng
Zhang, Qing
Zhao, Boxin
Li, Guofeng
A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats
title A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats
title_full A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats
title_fullStr A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats
title_full_unstemmed A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats
title_short A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats
title_sort novel berberine–glycyrrhizic acid complex formulation enhanced the prevention effect to doxorubicin-induced cardiotoxicity by pharmacokinetic modulation of berberine in rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353711/
https://www.ncbi.nlm.nih.gov/pubmed/35935857
http://dx.doi.org/10.3389/fphar.2022.891829
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